Regulation of Urea Synthesis : Changes in the Concentration of Ornithine in the Liver Corresponding to Changes in Urea Synthesis

Abstract

The biosynthesis of urea is regulated mainly by two factors, the amounts of urea cycle enzymes and the concentrations of acetyl-glutamate and ornithine. Schimke1 pointed out that the contents of all the urea cycle enzymes in the liver were directly proportional to the daily consumption of protein, then the activities of urea cycle enzymes are an important regulatory factor of the urea cycle. On the other hand, other investigators2–4 reported that the concentration of acetylglutamate, an allosteric activator of carbamylphosphate synthesis, and of ornithine, the rate limiting intermediate, changed under various dietary conditions and suggested that these amino acids play a role in the regulation of urea synthesis. We reported that ornithine and acetylglutamate play a more important role in the regulation of urea synthesis especially shortly after the dietary change. In the liver of rats subjected to acute dietary transitions from high to low protein or vice versa, the concentrations of ornithine and acetylglutamate changed greater and prior to the activity changes of urea cycle enzymes. The rate of urea synthesis from ammonium salt as a substrate were greatly changed in the perfused liver and correlated with the changes in the concentration of ornithine in the liver after the dietary changes5. Arginine derived from dietary protein is thought to be the main source of ornithine and also the cause of changes in acetylglutamate3–5. However, other factors must be involved in the regulation of the concentration of ornithine, since the concentration of orni-thine as well as acetylglutamate increased after the intraperitoneal injection of the ammonium salt without altering either arginine or protein input6.